Biological Activity and Use of Boron Compounds
Boron compounds are known to show a variety of different biological activities. Very often, boron compounds show enzyme inhibitory activity, and thus boron compounds can inhibit a number of enzymes alone or in a mixture with various co-inhibitors. For example, borates inhibit L-amino acid oxidase in a mixture with butanedione by interacting with the arginine residue in the active site. (Christman M F, Cardenas J M: Experientia 38 (5): 537-538 (1982)).
Similarly, borates and butanedione inhibit citrate/isocitrate-hydro-lyase, EC 4.2.1.3, again by interacting with the arginine residue from the active site. (Gawron O, Jones L: Biochem Biophys Acta 484 (2): 453-464 (1977)). Also, 2,3-butanedione or 1,2-cyclohexanedione in the presence of borates interact specifically with the guanidino group from arginine, and this fact was used for determination of arginine residues in the active site of the examined enzymes. In this way Dietl, T. and Tschesche, H. (Hoppe Seylers Z Physiol Chem: 357 (5): 657-665 (1976)) proved arginine residue is present in the active site of proteinases.
Borates (at low concentration) are also known to inhibit glyceraldehyde-3-phosphate dehydrogenase from human, pig and rabbit muscle. However, in greater concentration (above 6 mM) borates inhibit esterase and acetylphosphatase activities. (Wolny M: Eur J Biochem 80 (2): 551-556 (1977)).
An interesting biological activity of borates was noticed in the case of palytoxin induction of the histamine release from rat mast cells. In the presence of borates the activity of palytoxin was increased ten times (Chhatwal G S, Ahnert-Hilger G, Beress l, Habermann E: Int Arch Allergy Appl Immunol 68 (2): 97-100 (1982)).
Borates inhibit methylation of catechol estrogen and pyrocatechol by catechol-O-methyltransferase (Beattie J H, Weersink E: J Inorg Biochem 46 (3): 153-160 (1992)).
Several naturally occurring antibiotics contain boron as an essential structural element (such as boromycin, an anti-HIV antibiotic (Kohno J, et al: Biosci Biotechnol Biochem (Japan) 60(6), 1036-7 (1996), or tetralons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum (Irschik H, Schummer D, Gerth K, Hofle G, Reichenbach H: J Antibiot (Tokyo) (Japan), 48 (1), 26-30 (1995)).
Borates and some of their organic complexes are experimentally used in surgery as agents which promote healing of open wounds (Humzah M D, Marshall J, Breach N M: J R Coll Surg Edinb (England) 41(4), 269-70 (1996); McCowan M, Aitken F: J Wound Care (England), 6(5), 248-249 (1997); Bliss M R: J Wound Care (England) 6(5), 248-249 (1997)).
Larvicidal effects of ingestion of boric acid and disodium octaborate tetrahydrate by cat fleas was recently described by Hinkle N C, Koehler P G, and Patterson R S in J Med Entomol (United States), July 1995, 32(4), p 424-7.
Some specific organoboron compounds (such as cyanotriphenylborate) were shown to be subtype-specific blockers of glycine receptor chloride channels (Rundstrom N, Schmieden V, Betz H, Bormann J, Langosch D: Proc Natl Acad Sci USA (United States), 91(19), 8950-4 (1994)).
A very important biological behavior of certain boron compounds is their interaction with Ca-metabolism. Namely, it has been noticed (Benderdour M, Hess K, Dzondo-Gadet M, Dousset B: Biochem Biophys Res Commun 234 (1), 263-8 (1997)) that boric acid itself, acting upon a pelvic cartilage of chick embryo, induced release of proteoglycans, collagen and other proteins, but at the same time strongly decreased their intracellular synthesis. However, surprisingly enough, boric acid in the presence of a great molar excess of glucose did not decrease intracellular biosynthesis of proteins, but still induced efficiently their intensive secretion. The effect can not be ascribed to a boron toxicity, since the cell membranes were intact (observed by electronic microscopy) and the cells were secretory. It was assumed that boron interacted actively with Ca-metabolism (see, in addition to this article, Nielsen F, Muller L, Galigher S: J Trace Elem Exp Med 3, 45-54 (1990); Nielsen F H: FASEB 5, 2661-7 (1991)). Benderdour et al postulated that boric acid or its glucose complex can inhibit serine/threonine phosphatases.
Specific biological calcium-boron interaction is also supported by a work of T. Maruyama et al (J Biochem (Tokyo), 122(3), 498-505 (1997)) who showed that 2-aminoethoxydiphenyl borate (2 APB) inhibited Ins (1,4,5) P3-induced Ca2+ release from rat cerebellar microsomal preparations. At the same time, addition of 2 APB to the extracellular environment inhibited the cytosolic Ca2+ rise in intact cells such as human platelets and neutrophiles stimulated by thrombin or leukotriene B4 (LTB4).
Use Of Enzyme Inhibitors in the Negative Control of Hair Growth
Regarding the use of enzyme inhibitors for control of hair growth, there are several approaches described in the corresponding patent literature, all of which have nothing to do with boron. Patents describing an induction of hair re-growth are rather numerous and will not be discussed here. On the other hand, patents dealing with hair growth reduction, by inhibiting/targeting the key-enzymes which support/promote the hair growth, are not that numerous, but are of a particular relevance to our discovery.
For obvious reasons, in this overview of hair growth reduction, we ignore both classical depilation methods (using thio-glycolates, e.g.) and physical/mechanical methods of hair removal (such as laser treatment, e.g.).
In U.S. Pat. No. 4,885,289 (to M M Breuer et al, issued Dec. 5, 1989), a topical application of a steroid 5.alpha.-reductase inhibitor reduces male beard growth.
In U.S. Pat. No. 5,095,007 (to G S Ahluwalia, issued Mar. 10, 1992), the process of reducing the rate and altering the character of mammalian hair growth was described by topical application of a composition containing an inhibitor of adenylosuccinate synthetase.
In U.S. Pat. No. 5,096,911 (to G S Ahluwalia et al, issued Mar. 17, 1992) a reducing rate of mammalian hair growth was achieved by a topical application of a composition containing an inhibitor of gamma-glutamyl transpeptidase.
In U.S. Pat. No. 5,132,293 (to D Shander et al, issued Jul. 21, 1992) hair growth reduction was observed by topically applying an ornithine decarboxylase inhibitor.
In U.S. Pat. No. 5,143,925 (to D Shander and M G Funkhouser, issued Sep. 1, 1992) hair growth reduction was achieved by topical treatment of a mammalian skin with an inhibitor of the enzyme transglutaminase.
In U.S. Pat. No. 5,455,234 (to G S Ahluwalia and D Shander, issued Oct. 3, 1995), mammalian hair growth is reduced by applying to the skin an inhibitor of a cysteine synthesis pathway enzyme.
In U.S. Pat. No. 5,474,763 (to D Shander and G M Funkhouser, issued Dec. 12, 1995) mammalian hair growth is reduced by a topical application to the skin an inhibitor of ornithine aminotransferase.
In U.S. Pat. No. 5,468,476 (to G S Ahluwalia et al, issued Nov. 21, 1995), applying to the skin an inhibitor of nitric oxide synthetase reduced mammalian hair growth.
Finally, in U.S. Pat. No. 5,652,273 (to J. Henry et al, issued Jul. 29, 1997) a method of reducing hair growth in a mammal was described by applying a suppressor of the metabolic pathway for the conversion of glucose to acetyl-CoA.